Effect of xenon and argon inhalation on erythropoiesis and steroidogenesis: a systematic review

Abstract

BackgroundXenon and argon inhalation were included in the WADA Prohibited List in 2014 due to the reported positive effects on erythropoiesis. There has also been suggestions that steroidogenesis stimulation occurs as a result of the use of these substances. Currently, Xenon is on the WADA Prohibited List notable affecting erythropoiesis as a Hypoxia-inducible factor (HIF) activating agent. Thus, the systematic review of studies supporting these notions is of great interest.MethodsA thorough search for articles on the effects of Xenon and argon inhalation on erythropoiesis and steroidogenesis, as well as their negative effects on human health and methods of their detection in body fluids was conducted. Pubmed and Google Scholar databases were researched, as well as the special research section of the WADA website. The search was conducted in accordance with PRISMA guidelines. All articles in English published between 2000 and 2021 were analyzed, as well as reference studies meeting the search criteria.ResultsOnly two publications in healthy human subjects evaluating the effects of Xenon inhalation on erythropoiesis were found with no conclusive evidence of a positive effect on erythropoiesis. Both articles were published after 2014 when the gases were included on the WADA Prohibited List. Three more studies were conducted in animal models and one further study was conducted with human patients who had undergone Xenon anesthesia. There were no studies on the effect of argon inhalation on erythropoiesis. No studies were found on the effect of Xenon or argon inhalation on steroidogenesis in healthy subjects. No studies related to the effects of Xenon or argon inhalation on erythropoiesis and steroidogenesis were found on the WADA website.ConclusionThere is still inconclusive evidence to support the administration of Xenon and argon inhalations on erythropoiesis and steroidogenesis and their positive effects on health. Further research is needed to establish the effects of these gases. Additionally, improved communication between the anti-doping authorities and all key stakeholders is required to support the inclusion of various substances on the Prohibited List.

MiR-378a-3p and miR-491-5p as markers of xenon abuse in doping control

“…Ряд исследований показал [5,8,9], что при курсовом использовании ингаляций ксенона происходит активация транскрипционного фактора, индуцируемого гипоксией (HIF), и, соответственно, эритропоэтина (ЭПО), что потенциально может создавать преимущество применяющим его спортсменам. И хотя на этот счет в научной литературе приводятся довольно противоречивые данные [9,10,11], в 2014 году ВАДА ввело запрет на его использование, включив ксенон в статью S2 «Пептидные гормоны, факторы роста, подобные субстанции и миметики» [12]. В связи с этим перед антидопинговыми организациями встала проблема идентификации ксенона в допинг-пробах спортсменов.…”

Annual banned‐substance review 16th edition—Analytical approaches in human sports drug testing 2022/2023

“…PEPTIDE HORMONES, GROWTH FACTORS, RELATED SUBSTANCES, AND MIMETICS3.1 | EPO-receptor agonists (ERAs) and hypoxiainducible factor (HIF) activating agentsWithin the class S.2 of WADA's Prohibited List, ERAs represented 70% of all reported AAFs in 2021,126 suggesting that ERAs still play an important role as illicitly administered drugs in sport, despite the risks purportedly and evidently associated with their non-therapeutic use 133. Test methods regarding ERAs have been continuously optimized and complemented concerning enhanced anti-doping applications and additional strategies to determine the presence of a natural variant of EPO (c.577del) and in the light of medicinal research134 and pharmaceuticals potentially influencing the EPO biosynthesis in humans[135][136][137] To verify the presence of a single nucleotide polymorphism (SNP) in the c.577del EPO gene, which results in a frameshift and, consequently, in an increased molecular mass of the corresponding EPO protein, Yi et al presented a testing protocol a employing clustered regularly interspaced short palindromic repeats (CRISPR)/ dCas9-based testing approach 70. With designated primers, the relevant SNP-modified EPO sequence is polymerase chain reaction (PCR)amplified from 3 μL of blood and the amplicons and incubated with a complex formed from dCas9 and a variant-specific single-guide DNA.Only the variant amplicons bind to the ribonucleoprotein, which is subsequently visualized by native polyacrylamide gel electrophoresis and enables the identification of c.577del EPO gene variant carriers to support result interpretations of routine analyses concerning recombinant human EPO (rhEPO).…”